@misc{10481/93366,
year = {2024},
month = {5},
url = {https://hdl.handle.net/10481/93366},
abstract = {Even though morphological signs of differentiation have a minimal impact on survival after
intensive cytotoxic therapy for acute myeloid leukemia (AML), monocytic AML cell differentiation
(i.e., classified as French/American/British (FAB) subtypes M4/M5) is associated with a different
responsiveness both to Bcl-2 inhibition (decreased responsiveness) and possibly also bromodomain
inhibition (increased responsiveness). FAB-M4/M5 patients are heterogeneous with regard to genetic
abnormalities, even though monocytic differentiation is common for patients with Nucleophosmin
1 (NPM1) insertions/mutations; to further study the heterogeneity of FAB-M4/M5 patients
we did a proteomic and phosphoproteomic comparison of FAB-M4/M5 patients with (n = 13) and
without (n = 12) NPM1 mutations. The proteomic profile of NPM1-mutated FAB-M4/M5 patients
was characterized by increased levels of proteins involved in the regulation of endocytosis/vesicle
trafficking/organellar communication. In contrast, AML cells without NPM1 mutations were characterized
by increased levels of several proteins involved in the regulation of cytoplasmic translation,
including a large number of ribosomal proteins. The phosphoproteomic differences between the two
groups were less extensive but reflected similar differences. To conclude, even though FAB classification/
monocytic differentiation are associated with differences in responsiveness to new targeted
therapies (e.g., Bcl-2 inhibition), our results shows that FAB-M4/M5 patients are heterogeneous with
regard to important biological characteristics of the leukemic cells.},
organization = {Norwegian Cancer Society (grant no.
100933)},
organization = {Research Council of Norway INFRASTRUKTUR-program (project no. 295910)},
organization = {Proteomics
Unit at the University of Bergen (PROBE)},
publisher = {MDPI},
keywords = {Acute myeloid leukemia},
keywords = {Nucleophosmin 1 mutations},
keywords = {Differentiation},
title = {Monocytic Differentiation of Human Acute Myeloid Leukemia Cells: A Proteomic and Phosphoproteomic Comparison of FAB-M4/M5 Patients with and without Nucleophosmin 1 Mutations},
doi = {10.3390/ijms25105080},
author = {Selheim, Frode and Aasebø, Elise and Reikvam, Håkon and Bruserud, Øystein and Hernández Valladares, María del Carmen},
}